当前位置:  首页 >> 最新重要论文

最新重要论文

The hepatitis C virus protein NS3 suppresses TNF-a–stimulated activation of NF-kB by targeting LUBAC, Sci. Signal. 17 Nov 2015: Vol. 8, Issue 403, pp. ra118

发布时间:2016年01月25日

Science Signaling 17 Nov 2015: Vol. 8, Issue 403, pp. ra118 DOI: 10.1126/scisignal.aab2159

The hepatitis C virus protein NS3 suppresses TNF-a–stimulated activation of NF-kB by targeting LUBAC

Yongzhi Chen,1,2 Liang He,1,2 Yanan Peng,1,2 Xiaodong Shi,1 Jizheng Chen,3 Jin Zhong,4 Xinwen Chen,3 Genhong Cheng,1,5* Hongyu Deng1*

Abstract

The transcription factor nuclear factor kB (NF-kB) is crucial for innate immune defense against viral infections,  and its activation requires the ubiquitylation of upstream proteins, including the adaptor protein NEMO (NF-kB essential modulator). Many infectious pathogens, including hepatitis C virus (HCV), inhibit NF-kB signaling in host cells, which promotes pathogen survival. Frequently, HCV-infected individuals develop a chronic infection, which suggests that HCV can subvert host antiviral responses. We found that HCV infection and replication inhibited the activation of NF-kB by the inflammatory cytokine tumor necrosis factor–a (TNF-a), which was mediated by the viral protein NS3 and, to a lesser extent, NS5B. NS3 directly interacted with linear ubiquitin chain assembly complex (LUBAC), competed with NEMO for binding to LUBAC, and inhibited the LUBAC-mediated linear ubiquitylation of NEMO and the subsequent activation of NF-kB. Together, our results highlight an immune evasion strategy adopted by HCV to modulate host antiviral responses and enhance virus survival and persistence.

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201511/t20151130_4481197.html

文章链接:http://www.ibp.cas.cn/denghylab/denghylabkycg/201407/W020151119383889282859.pdf

 

 

    附件下载: